GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome

• DOI: 10.1038/s41467-022-34467-3
• Publication Date: 2022-11-08T20:11:51Z
• Authors: Silvia Tiberti; Carlotta Catozzi; Ottavio Croci; Mattia Ballerini; Danilo Cagnina; Chiara Soriani; Caterina Scirgolea; Zheng Gong; Jiatai He; Angeli D. Macandog; Amir Nabinejad; Carina B. Nava La...; Arianna Quinte’; Giovanni Bertalot; Wanda L. Petz; Simona P. Ravenda; Valerio Licursi; Paola Paci; Marco Rasponi; Luca Rotta; Nicola Fazio; Guangwen Ren; Uberto Fumagalli-...; Martin H. Schaefer; Stefano Campaner; Enrico Lugli; Luigi Nezi; Teresa Manzo
• Keywords: Tumor progression

CD8+ T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune impacts on clinical outcome is still its infancy. Here, we describe that interaction of tumor infiltrating neutrophils expressing high levels CD15 with effector memory (TEM) correlates progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes retention within increasing crosstalk cells. As consequence contact-mediated neutrophils, skewed to produce GZMK, which turn decreases E-cadherin intestinal epithelium and favors Overall, our results highlight emergence GZMKhigh TEM non-metastatic CRC tumors as hallmark driven by could implement current patient stratification be targeted novel therapeutics.